abrilumab (amg 181) in adults with moderate to severe crohn's disease

Conditions: Crohn's Disease

Summary: the primary objective of this study is to evaluate the efficacy of abrilumab as measured by the proportion of participants achieving crohn's disease activity index (cdai) remission (cdai \< 150) after treatment for 8 weeks.

the study consisted of a 24-week double-blind treatment period, a 108-week open-label treatment period, and a 2-year safety follow-up period. participants who did not reach minimal improvement, or experienced disease worsening after initial response, had the option to receive open-label abrilumab 210 mg every 3 months (q3m) beginning at double-blind period week 12 or after. not reaching minimal improvement was defined as not having an improvement in cdai score of ≥ 70 points from baseline on 2 consecutive visits (at or after week 8) at least 2 weeks apart. disease worsening after week 8 (or week 12) response was defined as having an increase in cdai score of ≥ 70 points from the week 8 (or week 12) cdai score on 2 consecutive visits at least 2 weeks apart, and a cdai score of \> 150. participants were planned to be randomized in a 2:1:2:1 ratio to sc placebo or abrilumab at 21 mg, 70 mg (on day 1, week 2, week 4, and every 4 weeks thereafter until week 24), or 210 mg (on day 1 followed by placebo in weeks 2 and 4 and every 4 weeks thereafter until week 24), respectively. due to a consistent discrepancy between the investigational product (ip) instruction manual (ipim) description of vial positions and the actual vial positions in the ip package participants were initially randomized to 3 arms (placebo, 70 mg, and 210 mg) with a randomization ratio of 3:2:1. the study was temporarily paused while this issue was investigated. once the discrepancy was corrected, protocol amendment 3 implemented, and affected participants completed their double-blind treatment period, the study resumed enrollment and randomization per protocol. neither the randomization nor study blind was compromised and therefore the intent-to-treat principle was maintained.

Eligibility criteria:
inclusion criteria: * diagnosed with ileal, ileo-colonic, or colonic crohn's disease for a minimum of 6 months prior to baseline * moderately to severely active crohn's disease defined by a cdai score ≥ 220 and ≤ 450 at baseline * evidence of active inflammation within 12 weeks prior to baseline * demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: immunomodulators and/or anti-tumor necrosis factor (tnf) agents or to corticosteroids (non-us sites only). * neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization * subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening exclusion criteria: * short bowel syndrome * stricture with obstructive symptoms within 3 months * bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline * ileostomy and/or colostomy * any gastric or intestinal pouch * evidence of an infected abscess * bowel perforation or evidence of non-inflammatory obstruction during the 6 months prior to baseline * stool positive for c. difficile toxin at screening * any uncontrolled or clinically significant systemic disease * known to have tested positive for hepatitis b virus surface antigen, hepatitis c virus antibody, or human immunodeficiency virus (hiv) * any underlying condition that predisposes subject to infections * subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline * received an anti-tnf agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods. * any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or tnf kinoid immunotherapies, amg 181, or any form of cell-based transplantation * received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals * significant laboratory abnormalities * pregnant or breast feeding

Keywords: ibd, crohn's disease